1. Field of the Invention
This invention relates to improved processes for preparing quinolinic acid, a starting material for the manufacture of nicotinic acid, vitamin B complex, and quinolinic acid anhydride, by first preparing copper quinolinate by oxidizing quinoline with hydrogen peroxide in an aqueous sulfuric acid medium in the presence of a copper sulfate, and in subsequent steps converting said copper quinolinate to quinolinic acid by precipitating the copper as an insoluble salt in an alkaline medium and acidifying the resulting alkaline salt of quinolinic acid.
2. Description of the Prior Art
There are several synthetic routes described in the prior art for the preparation of copper quinolinate and the conversion thereof to quinolinic acid via precipitation of the copper as insoluble cupric salts. One of these routes, and the one in which this invention constitutes an improvement, involves the oxidation of quinoline with hydrogen peroxide in a very dilute aqueous acid medium in the presence of a copper salt and the subsequent conversion to quinolinic acid via alkaline precipitation of the copper as cupric sulfide followed by acidification of the alkaline salt of the quinolinic acid. The following items, which are based on the oxidation of quinoline and subsequent conversion to quinolinic acid, to date appear to constitute the most relevant prior art with regard to the instant invention.
W. Stix and S. A. Bulgatsch in Chemische Berichte, 65, 11 (1932) [Chemical Abstracts 26: 2195.sup.1 (1932)]describe the preparation of copper quinolinate by the oxidation of quinoline. In their process, Stix and Bulgatsch heat a mixture of quinoline, three percent aqueous hydrogen peroxide and 25 percent aqueous copper sulfate solution in one large portion while maintaining a temperature maximum of 70.degree. C. with external cooling. The reaction is maintained at 70.degree. C. for eight hours and additional hydrogen peroxide is added and the temperature maintained. Alkali is added to the solution to reduce the acidity and after heating to 90.degree. C. the reaction is cooled to room temperature to obtain copper quinolinate in 67 percent yield based on the quinoline used. The copper quinolinate was then reacted with ten percent aqueous sodium sulfide, and after the insoluble copper sulfide was removed by filtration, the resulting solution was made acid with sulfuric acid to obtain quinolinic acid of indeterminate purity in 51.5 percent yield based on the quinoline used.
U.S. Pat. No. 2,371,691, which issued Mar. 2, 1945 in the names of A. T. Hawkinson and A. A. Elston, teaches the preparation of copper quinolinate by slowly adding hydrogen peroxide to a solution of quinoline, copper acetate, acetic acid and water at 60.degree. C. at such a rate as to maintain the reaction mixture temperature below 70.degree. C. Copper quinolinate is obtained in 69.1 percent yield based on the quinoline used.
U.S. Pat. No. 2,347,410, which issued Apr. 25, 1944 in the names of A. T. Hawkinson and A. A. Elston, teaches a process for the manufacture of pyridine carboxylic acids, especially quinolinic and nicotinic acids, from their heavy metal salts, especially copper salts. The copper quinolinate dihydrate is first suspended in sufficient water to form a thin slurry and with agitation concentrated ammonium hydroxide is added in a sufficient amount to cause complete solution of the copper quinolinate. The resulting solution is treated with an excess of sodium hydroxide solution. The solution is then heated in the range of 40.degree. to 60.degree. C. to form and precipitate the copper oxide which is collected by filtration. The filtrate containing the alkali salt of quinolinic acid is boiled to remove the excess ammonia. The solution is adjusted to a pH in the range of 3 to 5 with a mineral acid and the resulting solution is evaporated to dryness to obtain a mixture of quinolinic acid and salts.